This project is based on a comparison of sodium potassium ionic currents which underlie excitability in nerve and heart cell membranes. The experimental preparations used in this work include squid giant axons and embryonic heart cells. Measurements of membrane current kinetics and rectifier properties in these cells have been described. For example, the currents which underlie the repolarization phase of the action potential in embryonic heart cells have recently been determined. Two potassium currents are involved in this process. One component is similar to potassium current in nerve; the other component is similar to the inward rectifier of skeletal muscle. These results have been incorporated into mathematical models which have been used to simulate heart cell excitability. Potassium current kinetics have also been measured in squid axons with a particular emphasis on the effects of external potassium ions on potassium current kinetics. These basic studies provide a framework for analyses of the effects of drugs on nerve and cardiac tissues. For example, the mechanism of antifibrillatory drug action on the heart has recently been investigated. Antifibrillatory compounds, such as bretylium tosylate, produce a marked blockade of potassium current in squid axons. Other drugs, such as lidocaine, which do not produce a strong antifibrillatory action on the heart, do not produce a significant block of potassium current. These results suggest that modification of the potassium component are important in the treatment of some cardiac arrhythmias.